Aralkylaminoalkylene guanidines



United States Patent F 3,211,789 ARALKYLAMINOALKYLENE GUANIDINES Nils S. Hjelte, Svartbacksgatan 101A, Uppsala, Sweden No Drawing.v Filed Dec. 27, 1962, Ser. No. 247,553 Claims priority, application Sweden, Aug. 23, 1962,

9,136/ 62 p 19 Claims. (Cl. 260'564)- INTRODUCTION The present invention generally relates to novel guanidine derivatives and acid-addition salts thereof. More particularly, the invention pertains to N-(guanidinoalkyD- N-alkyl phenyl alkyIamineS and substitution products of these compounds carrying one or more substituents in the phenyl radical as well as acid-addition salts thereof.

THENOVEL GUANIDINE DERIVATIVES BROADLY The novel guanidine compounds of this invention can be represented by the formula:

wherein:

R. represents. at least one member selected. from the. group consisting of hydrogen, halogen, lower alkyl, and lower alkoxy, R is a lower alkyl, containing from 1 to 4, inclusive, carbon atoms, B is a lower alkylene, containing from 2 to 5, inclusive, carbon atoms, and A is a lower alkylene, containing from 1' to 5, inclusive, carbon atoms, and non-toxic acid-addition salts thereof. The number of possible substituents in the phenyl radical is arbitrary. The substituent, if any, is usually in the para-position of the phenyl radical, but may also be present in the ortho-position.

As examples ofthe substituents R, R A and B in the aboveformula there may be mentioned:

R2. hydrogen, chloro, bromo, methyl, ethyl, propyl, isopropyl, n-butyl,.isobutyl, sec.butyl,tert.butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec.butoxy, isobutoxy,

R methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl,

sec.buty1, tert.butyl,

B: 1,2-ethylene, 1,3-propylene-, 1-methyl-1,2-ethylene, 2- methyI-LZ-ethylene, 1,4-butylene, 1,l-dimethyl-1',2- ethylene, 2-methyl-1,3-propylene, 1-methyl-1,3-propylene, 3-methyl-1,3-propylene, 1,5-pentylene, 1-methyl-l,4- butylene,

A: 1,2-ethyl'ene, 1,3-propylene, 1-methyl-1,2-ethylene, 2-

methyl-1,2-ethylene, 1,4-butylene, 2-methyl-1,3-propylene, 1,5-pentylene,1-methyl-l,4-butylene, 4-methyl-1,4- butylene- Specific compounds encompassed by the above formula are set forth in the following examples and claims.

FREE. BASES OR ACID-ADDITION SALTS OF THE NOVEL GUANIDINE DERIVATIVES Depending on the conditions used, the novel guanidine derivatives of this invention can be obtained in the form of their free bases or their salts. The salts can be converted, in a known manner, to their corresponding free bases, for example by reacting them with a basic substance, such as an alkali metalhydroxide or an alkali metal carbonate. The free base canbeconverted into its acid-addition salts, for example byreacting. it: with an inorganic or organic acid according to procedures well known to the art (see for example U.S.P. 2,928,829, column 3, line 33 to column 4, line 1 0)". A solvent can be present during the salt forming: operation- Ion exchangers may also be utilized to effectthe above conversions.

UTILITY OF THE NOVEL GUANIDINE DERIVATIVES The above-mentioned novel guanidine derivatives. and their salts, especially the mono-acid-addition salts, exhibit a rapidly beginning blocking effect on the sympathetic nervous system of long duration without any essential effect on the parasympathetic nervoussystem. They are, therefore, especially valuable blood-pressure lowering agents.

The novel compounds of this invention can be administered as suchor in the form of their salts, if desired, after compounding them with pharmaceutically usable ad'- juvants and carriers, parenterally or orally. For the oral administration may be mentioned tablets and d'rages into which the compounds are converted by mixing them with the usual carriers, such as milk, sugar, starch, tragacanth and magnesium stearate. Any well known medicament compounding or administering procedure can be used. (e.g. see U.S.P. 2,928,829,, column 4, line 60 to. column 5, line 4).

GENERAL PREPARATION OF THE NOVEL. GUANIDINE DERIVATIVES The novel guanidine derivatives are prepared by treating a first reactant, comprising an amine of the formula:

R in which R, R A and B each have the above-mentioned significance, with a second reactant capable of forming, with the primary amino-group of the first reactant by condensation or addition, the guanidino group and then converting, if desired, the resulting reaction product into its acid-addition salts with inorganic or organic acids.

EXAMPLES IN GENERAL The following examples are illustrative of preferred embodiments of' the present invention. It should be understood that these examples are not intended to limit the invention and that obvious changes. may be made by those skilled in the art without changing the essential characteristics and the basic concept of the invention. The parts and percentages are by weight, the degrees are in Centigrade, the temperature is room temperature, and the pressure is atmospheric, unless otherwise indicated.

Example 1.-N (2 guanidinoethyl) N methyl 3- phenylpropylamine (A) N methyl N cyanomethyl 3 phenylpropyl amine.-In a flask are placed a mixture of 19.6 g. (0.26 mole) of chloroacetonitrile and 17.9 g. (0.13 mole) of sodium carbonate in 200 ml. of benzene and to the mixture is added, dropwise, a solution of 39 g. of N-methyl- 3-phenylpropylamine in ml. of benzene. The mixture is heated with reflux for 10 hours. After filtration, the sol-vent is driven off from the filtrate and the residue is distilled under vacuum collecting a fractionhaving the B.P. 118-120 at 1.0 mm. of Hg, n =l.5132. The yield of N-methyl-N-cyanomethyl-3-phenylpropylamine is 28.5 g. (58 percent).

(B) N methyl N (2 aminoethyl) 3 phenylpr0pylamine.A solution of 28.5 g.. (0.15. mole) of N- methyl-N-cyanomethyl-3-phenylpropylamine in 5.0 ml. of dry ether is added dropwise to 8.7 g, (0.23 mole) of lithiumaluminiumhydride, dispersed in 400. ml. of dry ether. The mixture is refluxed for 4 hours. After hydrolyzing and filtration ofthe aluminate formed thereby, and evaporation of the solvent from the filtrate, the residue is distilled while collecting a fraction having the B.P. 139-144 C. at 8 mm. of Hg, n =1.5158. The

Patented Oct, 1-2, 1965 H N i S Calculated Found Example 2.N (2 guanidinoethyl) N methyl 2- phenyl-I-methylethylamine (A) N cyanomethyl N methyl 2 phenyl 1- methylethylamine.30 g. (0.2 mole) of N methyl 2- phenyl-l-methylethylamine, dissolved in 60 ml. of benzene, are added to a mixture of 15.1 g. (0.2 mole) of chloroacetonitrile in 100 ml. of benzene and 10.6 g. (0.1 mole) of sodium carbonate during about 30 min., and the mixture is refluxed for 4 hours. On cooling, all solids are filtered off and the filtrate is evaporated. The residue is distilled under vacuum. In this connection, a fraction having the B.P. 165 C. at 10 mm. of Hg, n =1.5179, will be obtained. The yield of N-cyanomethyl-N-methyl- 2-phenyl-l-methylethylamine will be 28 g. (81.5%).

(B) N (2 aminoethyl) N methyl 2 phenyl 1- methylethylamine.-28 g. of N-cyanomethyl-N-methyl-2- phenyl-l-methylethylamine (0.159 mole) are dissolved in 100 ml. of dry ether and the solution is added, in a dropwise manner, to 9.5 g. (0.25 mole) of lithiumaluminiumhydride, dispersed in 400 ml. of dry ether. The mixture is refluxed for 5 hours. After hydrolyzing, filtering the aluminate formed as a result hereof, drying the filtrate and evaporating the latter, the residue is distilled under vacuum while collecting a fraction having the B.P. 125- 135 C. at mm. of Hg. The yield of N-(Z-aminoethyl)-N-methyl-2-phenyl-l-methylethylamine will be 19 g. (62%). (C) N (2 guanidinoethyl) N methyl 2 phenyl- 1-methylethylamine.-19 g. (0.105 mole) of N-(Z-aminoethyl)-N-methyl-2-phenyl-l-methylethylamine and 13.9 g. (0.053 mole) of S-methyl-carbamide-sulfate are dissolved in 200 ml. of water and the solution is refluxed for 4 hours. On cooling, crystallization will take place. The crystallizate is recrystallized from ethyl alcohol. The yield of bis-[N-(2-guanidinoethyl)-N-methyl-2-phenyl1- methylethylamine]-sulfate is 22 g. (74 percent); melting point 176178 C.

Analysis:

1 o H I N s Calculated 55. 10 8. 18 19. 77 5.66 Found 55. 44 8.37 19. 96; 19. 92 5. 56

Example 3.N-(2-guanidin0ethyl) -N-methyl- 2-phenylethylamine 4 under vacuum to collect a fraction having the B.P. C. at 0.3 mm. of Hg, n =1.5186. The yield of N-methyl-N-cyanomethyl-Z-phenylethylamine will be 60 g. (86% (B) N methyl N (2 aminoethyl)-2-phenylethylamine.30 g. (0.18 mole) of N-methyl-N-cyanomethyl-2- phenylethylamine are dissolved in 100 ml. of dry ether and the solution is added to 8.5 g. (0.23 mole) of lithiumaluminiumhydride, dispersed in 500 ml. of dry ether. The mixture is refluxed for 10 hours. After hydrolyzing and filtering off the aluminate, the filtrate is evaporated and the residue is distilled under vacuum to collect a fraction having the B.P. 129-132 C. at 10 mm. of Hg, n =1.5212. The yield of N-rnethyl-N-(Z- aminoethyl)-2-phenylethylamine is 28.0 g. (87.5%).

(C) N-(Z-guanidinoethyl)-N-methyl 2 phenylethylamine-28 g. (0.15 mole) of N-methyl-N-(Z-aminoethyl)-2-phenylethy1amine and 21.75 g. (0.075 mole) of S-methylthiocarbamidesulfate are dissolved in 130 ml. of water and the solution formed is refluxed for 4 hours. On cooling, crystallization will take place. The crysta1- lized product is recrystallized from a mixture of alcohol and ether. The yield of bis-[N-(2-guanidinoethyl)-N- methyl-2-phenylethylamine]-sulfate is 32.5 g. (81.5%) having the melting point 167l68 C.

Example 4.N-(2-guaniainoethyl)-N-ethyl-3- phenylpropylamine (A) N cyan0methyl-N-ethyl-3-phenylpr0pylamine. 26 g. (0.16 mole) of N-ethyl-3-phenylpropylamine are added, in a dropwise manner, to a mixture of 8.5 g. (0.08 mole) of sodiumcarbonate and 12.3 g. (0.16 mole) of chloroacetonitrile in 200 ml. of absolute ethyl alcohol. The mixture is refluxed for 6 /2 hours and is then left to stand overnight at room temperature. The sodium chloride formed is separated off, the filtrate is evaporated, and the residue distilled under vacuum while collecting a fraction having the B.P. 168 C. at 10 mm. of Hg, n =1.5089. The yield of N-cyanomethyl-N-ethyl-Iiphenylpropylamine is 28 g. (87%).

(B) N-(Z-aminoethyl)-N-ethyl-3phenylpropylamine- 28 g. (0.13 mole) of N-cyanomethyl-N-ethyl-3phenylpropylamine are dissolved in 50 ml. of dry ether and the solution is added, in a dropwise manner, to 6.5 g. (0.17 mole) of lithiumaluminiumhydride in 500 ml. of ether. The mixture is refluxed for 10 hours. After hydrolyzing, the aluminate is separated off and the filtrate is evaporated, whereupon the residue is destilled under vacuum while collecting a fraction having the B.P. -178 C. at 10 mm. of Hg. The yield of N-(Z-aminoethyl)-N-ethyl-3- phenylpropylamine is 24.1 g.

(C) N-ethyI-N-(Z-guanidinoethyl) 3 phenylpropylamine.-24.1 g. (0.117 mole) of N-(2-aminoethyl)-N- ethyl-3-phenylpropylamine and 16.1 g. (0.0585 mole) of S-methylthiocarbamidesulfate are dissolved in 200 ml. of water and the solution is heated for 6 /2 hours with reflux. On cooling, crystallization will take place, and the crystals are then filtered off. They are recrystallized from a mixture of ethyl alcohol and water to yield 18 g. of bis-[N-ethyl-N-(Z-guanidinoethyl) 3 phenylpropylamine] -sulfate having the melting point 73-75 C.

Example 5 .N (3-guanidin0pr0pyl -N -methyl-3- phenylpropylamine (A) N-(2 cyanoethyl) N methyl-3-phenylpropylamine.17 g. (0.115 mole) of N-methyl-3-phenylpropylamine are added, in a dropwise manner, to 6.1 g. (0.115

mole) of acrylnitrile at room temperature. The mixture is then heated on a water bath for 4 hours and left to stand over night. The product is distilled under vacuum to collect a fraction having the B.P. 175-177 C. at mm., n =l.5132. The yield of N-(2-cyanoethyl)-N-3- phenylpropylamine is 20 g. (86% (B) N-(3-amin0propyl)-N-methyl 3 phenylpropylamine.20 g. (0.099 mole) of N-(Z-cyanoethyD-N- methyl-3-phenylpropylamine are dissolved in 50 ml. of dry ether and to the solution is added a dispersion of 4.95 g. (0.13 mole) of lithiumaluminiumhydride in 300 ml. of dry ether. The reaction mixture is refluxed for 6 hours and is then left to stand over night at room temperature. After hydrolyzing, the hydroxide is separated ofl and the filtrate is evaporated. The residue is distilled under vacuum while collecting a fraction having the B.P. 154-156 C. at 10 mm. of Hg, n "=1.5140. The yield of N-(3-aminopropyl)-N-methyl-3-phenylpropylamine is 11 g.

(C) N-(3-guanidinopropyl)-N-methyl-3-phenylpr0pylamine.11 g. (0.0535 mole) of N-(3-amino-propyl)-N- methyl-3-phenylpropylamine and 7.4 g. (0.0268 mole) of S-methylthiocarbarnidesulfate are dissolved in 75 ml. of water and the solution is refluxed for 6 hours. After cooling, the product is recrystallized from alcohol. The yield of bis-[N-(3-guanidino-propyl)-N-methyl-3-phenylpropylamine1-sulfate is 14 g.; melting point 109-414 C.

Example 6 .N (Z-guanz'dinoethyl -N -methyl-3- p-methoxypheny-l -pr0pylamine (A) N-cyan0methyl-N-methyl-3 (p-methoxyphenyly pr0pylamine.-A mixture of 23.6 g. (0.315 mole) of chloroacetonitrile and 16.8 g. (0.158 mole) of sodium carbonate in 500 ml. of absolute alcohol is added, in a dropwise manner, to 56 g. (0.315 mole) of N-methyl-3- (p-methoxyphenyl)-propylamine. The reaction mixture is refluxed for 6 hours. After cooling, the sodium chloride formed is separated off. The filtrate is evaporated and the residue is distilled under vacuum while collecting a fraction having the B.P. 155-165 C. at 0.3 mm. of Hg. The yield of N-cyanomethyl-N-methyl-3-(p-methoxyphenyl)-propylamine is 59 g.

(B) N-(Z-aminoethyl)-N-methyl-3-(p-methovcyphenyl)- pr0pylamine.--To 59 g. (0.27 mole) of N-cyano-methyl- N-rnethyl-3-(p-methoxyphenol)-propylamine are added 12.5 g. (0.33 mole) of lithiumaluminiumhydride, dispersed in 1000 ml. of dry ether, in a dropwise manner. The reaction mixture is refluxed for 8% hours to cause hydrolyzing to take place. The hydroxide is filtered otf, the filtrate is evaporated, and the residue is distilled under vacuum to collect a fraction having the B.P. 108-111 C. at 10 mm. of Hg, n =l.5203. The yield of N-(2- aminoethyl)-N-methyl 3 (p methoxy-phenyl)-propylamine is 23.5 g.

(C) N-(Z-guanidinoethyl)-N-methyl-3-(p-methoxyphevzyl)-pr0pylamine.23.5 g. (0.111 mole) of N-(Z-aminoethyl) -N-methyl-3- (p-methoxyphenyl) -propylamine and 15.2 g. (0.055 mole) of S-methylthiocarbamidesulfate are dissolved in 150 ml. of water and the mixture is heated for 8 hours. After cooling, the reaction product will crystallize. After recrystallization of the latter, there is obtained 6 g. of bis-[N(2-guanidinoethyl)-N-methyl-3- (p-methoxyphenyl) -propylamine]-sulfate having the melting point 149-151 C.

Example 7 .--N-methyl-N-(Z-guanidinoethyl )-3-(pchlorophenyl) -p-r0pylam'ine (A) N-cyanomethy'l-N-methyl-3-(p-chl0r0phenyl) -pr0- pylamine.-A mixture of 29.6 g. of chloroacetonitrile and 29.8 g. (0.196 mole) of sodium carbonate in 500 ml. of absolute ethyl alcohol is added dropwise to 42 g. (0.392 mole) of N-methyl-3-(p-chlorophenyl)-propylamine. The reaction mixture is refluxed for 7 hours. Oncooling, the sodium chloride is separated ofi. The filtrate is evaporated and the residue is distilled under vacuum while collecting a fraction having the B.P. 153-157 C. at 0.2 mm. of Hg. The yield of N-cyanornethyl-N-methyl-3-(p-chlorophenyl)-propylamine is 81.5 g.

(B) N-(Z-aminoethyl)-N-methyl-3 (p-chlorophenyD- propylamine-To 81.5 g. (0.377 mole) of N-cyano-methyl-N-methy1-3-(p-chlorophenyl) propylamine are added 23.0 g. (0.55 mole) of lithiumaluminiumhydride, dispersed in 1500 ml. of dry ether, dropwise. The reaction mixture is refluxed for 8% hours, whereupon hydrolyzing is carried out. The hydroxide is filtered 011?, the filtrate is evaporated and the residue is distilled under vacuum while collecting a fraction having the B.P. 164168 C. at 10 mm. of Hg, n =1.5288. The yield of N-(2- aminoethyl)-N-methyl-3-(p-chlorophenyl)-propylamine is 45.5 g.

(C) N-(Z-guanidinoethyl)-N-methyl-3-(p-chl0r0phenyl)-propylamine.45.5 g. (0.201 mole) of N-(Z-aminoethyl)-N-methyl-3-(p chlorophenyl) propylamine and 27.8 g. (0.100 mole) of S-methylthiocarbamidesulfate are dissolved in 250 ml. of water, and the mixture is heated With boiling for 5 hours. On cooling, the reaction prod not will crystallize. After recrystallization of the latter, there will be obtained 52 g. of bis-[N-(Z-guanidinoethyD- N-methyl-3- (p-chloro-phenyl) propylamine] -sulfate having the melting point 161163 C.

Example 8.N-(Z-guanidinoethyl)-N-methyl-3- (2- bromophenyl) -propylamine (A) N-cyanomethyl-N-methyl-3- (2-bromophenyl) -propylamine.14 g. (0.0614 mole) of N-methyl-3-(2-bromophenyU-propylamine, dissolved in 50 ml. of absolute ethyl alcohol, are added to 3.3 g. (0.0307 mole) of sodium carbonate and 4.64 g. (0.0614 mole) of chloroacetonitrile in 150 ml. of absolute ethyl alcohol. The mixture is refluxed with agitation for 17 hours. After cooling, the sodium chloride is filtered off, and the ethyl alcohol is driven off. The residue is dissolved in diethylether and washed with water. The ether phase is dried, and the solvent is then driven off. The product is distilled collecting a fraction having the B.P. 148-152 C. at 0.5 mm. of Hg, n =1.5439. The yield of N-cyanomethyl-N- methyl 3 (2 bromophenyD-pr-opylamine is 13.5 g. (82.5

(B) N (2 am'inoethyl) N methyl -.3 (2 bromophenyl)-pr0pylamine.-13.5 g. (0.0505 mole) of N-cyanomethyl-N-methyl-3-(2-bromophenyl)propylamine, dissolved in 50 ml. of dried ether, are added, dropwise, to 2.48 g. (0.065 mole) of lithiumaluminiumhydride, dispersed in 200 m1. of dry ether. The mixture is refluxed with agitation for 18 hours. After hydrolyzing, the aluminate is filtered oft and Washed four times with ether. The ether extracts are dried and evaporated. The residue is distilled under vacuum while collectinga fraction having the B.P. 130 C. at 0.3 mm. of Hg, n =1.5451. The yield of -N-(2-aminoethyl)-N-methyl-3 (2-bromophenyl)-propylamine is 11.5 g. (84% (C) N (2 guanidinoethyl) N methyl 3 (2 bromophenyl)propylamine-4 1.5 g. (0.0425 mole) of N-(2- aminoethyl)-N-methyl-3-(2-bromopheny1) propylamine and 5.9 g. (0.0212 mole) of S-methylisothiocarbamidesulfate, dissolved in 50 ml. of water, are refluxed for 6 hours. On cooling, the reaction product will crystallize. The crystallizate is first recrystallized from Water and then from a mixture of methanol and acetone. The yield of his [N (2 guanidinoethyl) N methyl 3 (2 bromophenyl)-propylamine]-sulfate having the melting point 162-164 C. is 10.2 g.

Analysis-Cale. C, 43.10; H, 6.12; N, 15.47; S, 4.42; Br, 22.06. Found: C, 43.16; H, 6.15; N, 15.46; S, 4.78; Br, 21.81.

Example 9.N(2-guanidinoethyl)-N-methyl-3-(2- chlorophenyl) -pr0pylamine (A) N cyzmomethyl N methyl 3 (2 chlorophenyl) -prop ylamine.-42.3 g. (0.232 mole) of N-methyl-3- (2-chlorophenyl)-propylamine, dissolved in 50 ml. of absolute ethyl alcohol, are added in a dropwise manner to 17.5 g. (0.232 mole) of chloroacetonitrile and 12.3 g. (0.116 mole) of sodium carbonate in 450 ml. of absolute ethyl alcohol. The mixture is refluxed for 8 hours with agitation. After cooling, the sodium chloride is filtered off and the ethyl alcohol is driven off. The residue is dissolved in diethyl ether and rinsed with water. The ether phase is dried, and the ether is driven off. The residue is distilled under vacuum while collecting a fraction having the BF. 172l76 C. at 10 mm. of Hg, n =1.5269. The yield of N-cyanomethyl-N-methyl-3-(2-chlorophenyl)-propylamine is 42 g. (82% (B) N (2 aminoethyl) N- methyl 3 (2 chloroplzenyl)-prpyl|amine.42 g. (0.189 mole) of N-cyanomethyl N methy-3-(2-chlorophenyl)-propylamine dissolved in 100 ml. of dried diethylether, are added, in a dropwise manner, to 9.5 g. (0.25 mole) of lithiumaluminiumhydride dispersed in 700 ml. of dried ethylether. The mixture is refluxed for 8 hours. After hydrolyzing, the aluminate formed is filtered off and rinsed four times with diethylether. The ether phases are combined and dried. The ether is driven off and the residue is distilled in vacuum while collecting a fraction having the 13.1. 153157 C. at 10 mm. of Hg, n =1.5292. The yield of N (Z-aminoethyl)-N-methyl-3-(2-chlorophenyl)-propylamine is 35.5 g. (84%).

(C) N (2 guanidinoethyl) N methyl 3 (2- chlorophenyl)-pr0pylamine.l7.9 g. (0.0792 mole) of N (2 aminoethyl) N methyl 3 (2 chlorophenyl) propylamine and 11 g. (0.0396 mole) of S-methyl-isothiocarbamidesulfate are dissolved in 50 ml. of water, and the solution is refluxed for 7 hours. On cooling, the product will crystallize. The crystallizate is first recrystallized from water and then from a mixture of methanol and acetone. The yield of bis-[N-(Z-guanidinoethyl)-N-methyl- 3-(2-chlorophenyl)-propylamine]-sulfate having the melting point 176.5l78 C. is 11.1 g.

Analysis.-Calc.: C, 49.12; H, 6.98; N, 17.04; S, 5.04; Cl, 11.16. Found: C, 49.11; H, 6.87; N, 17.58; S, 5.22; CI, 11.20.

What is claimed is: t

1. A member of the group consisting of (1) compounds of the formula:

in which R represents a member selected from the group consisting of hydrogen, chloro, bromo, and lower alkoxy, R is a lower alkyl, containing from 1 to 4, inclusive, carbon atoms, B is a lower alkylene, containing from 2 to 5, inclusive, carbon atoms, and A is a lower alkylene, containing from 1 to 5, inclusive, carbon atoms, and (2) therapeutically useful acid-addition salts of said compounds.

Z. N (2 guanidinoethyl) N methyl 3 phenylpropylamine.

3. Therapeutically useful acid-addition salts of the compound set forth in claim 2.

4. N (2 guanidinoethyl) N methyl 2 phenyl 1- methylethylarnine.

5. Therapeutically useful acid-addition salts of the compound set forth in claim 4.

6. N (2 guanidinoethyl) N methyl 2 -phenylethylamine.

7. Therapeutically useful acid-addition salts of the compound set forth in claim 6.

8. N (2 guanidinoethyl) N ethyl 3 phenylpropylamine.

9. Therapeutically useful acid-addition salts of the compound set forth in claim 8.

10. N (3 guanidinopropyl) N methyl 3 phenylpropylamine.

1'1. Therapeutically useful acid-addition salts of the compound set forth in claim 10.

12. N (2 guanidinoethyl) N methyl 3 (p methoxyphenyD-propylarnine.

-13. Therapeutically useful acid-addition salts of the compound set forth in claim 12.

14. N (2 guanidinoethyl) N methyl 3 (p chlorophenyl)-propylamine.

15. Therapeutically useful acid-addition salts of the compound set forth in claim -14.

16. N (2 guanidinoethyl) N methyl 3 (o chlorophenyl)-propylamine.

17. Therapeutically useful acid-addition salts of the compound set forth in claim 16.

18. N (2 guanidinoethyl) N methyl 3 (o bromophenyl)-propylamine.

I19. Therapeutically useful acid-addition salts of the compound set forth in claim 18.

References Cited by the Examiner UNITED STATES PATENTS 2,672,029- 6/28 Heyn 260564 2,851,457 9/58' Zimmermann 260243 2,881,175 4/591 Wright 260294.7 2,903,453 9/59 Biel 260247.2 2,928,829] 3/60 Mull 260239 2,951,078 8/60 Biel 260247.5 3,006,913 10/61l Mull 260-239 3,027,370 3/62 Bindler 260564 X CHARLES B. PARKER, Primary Examiner. 

1. A MEMBER OF THE GROUP CONSISTING OF (1) COMPOUNDS OF THE FORMULA: 